Comparison of serum neopterin levels and urinary neopterin excretion in renal allograft recipients.

Determination of serum and urinary neopterin levels was performed daily in 30 patients undergoing kidney transplantation for treatment of end-stage renal failure. Neopterin serum levels were determined by RIA and urinary excretion by HPLC. In parallel, the same samples were tested for creatinine content. Results indicated a strong correlation between the clearance of neopterin and creatinine. This correlation was independent of the extent of functional impairment as well as of the different causes of renal insufficiency. As a consequence, a strong relationship between serum and urinary neopterin levels was only obtained when values were corrected for different renal function by dividing them by the creatinine levels. It thus appears that major attention has to be paid to the functional state of the kidney when studying neopterin serum and/or urine values. It also appears that under these prerequisites both methods of detection as well as both sample sources yield comparable results.

[Endemic goiter in Austria's youth?]. / Gibt es noch eine Kropfendemie bei Osterreichs Jugend?

After 17 years the efficiency of iodine prophylaxis of endemic goiter (1 : 100000) in Austria was checked by control field studies in 3 Tyrolean towns n Austria. The data obtained there were compared with those of 123 school age children from the iodine deficient endemic goiter area of the province of Bolzano (Italy). The results show a reduction in goiter incidence from 50 to 35% in the total population in Austria, where goiter incidence in schoolchildren dropped from 45.9% to 12%. Urinary iodine/g creatinine was 65 micrograms in Austria, the 24 hr radioiodine uptake with 41.8% was normal. In comparison the ethnologically and geographically similar endemic goiter zone in the province of Bolzano showed a goiter incidence in schoolchildren of up to 46%, while urinary iodine/g creatinine was 35.9 micrograms and radioiodine uptake after 24 hr about 50%. Extensive studies of peripheral hormone parameters (T4, TBG, T3, TSH, rT3, FT3, FT4) revealed a significantly higher rT3 concentration of 24.7 ng/dl in Austria compared with a value of only 19.8 ng/dl in the province of Bolzano. These facts suggest an increased conversion of T4 to real T3 in iodine deficiency, which might contribute to the adaptation of the organism to this condition. No statement, however, can be presented regarding the regulation of this phenomenon. Even as endemic goiter is decreasing in Austria, an increase of salt iodization to 1 : 50000 according to the swiss procedure might eliminate definitely endemic goiter in Austria.

[Thyroid proteins in endemic goitre and their relationship to the intrathyroidal thyroid hormone concentration]. / Schilddrüsenproteine in endemischen Strumen und ihre Beziehung zur intrathyreoidalen Schilddrüsenhormonkonzentration.

According to several reports we suspected that the pathogenesis of endemic goitre cannot be explained by iodine deficiency only, but that other--partially endogenous--goitrogenic factors must be present. We therefore studied 16 cases of "euthyroid" endemic goitre from the endemic goitre area of the province of Bolzano in Italy. After fractionation of tissue homogenates, T 4 and T 3 were measured by RIA and the I concentration was also termined. Thyroglobulin and its fractions were measured by ultracentrifuge procedures after assessment of the total protein concentration. Evaluation of the present results suggests that an insufficient synthesis of thyroglobulin in the examined goitres induces an inadequate adaptation of the organism to iodine deficiency, which, in turn, decreases the thyroid hormone concentration in thyroid tissue and enhances goitrogenesis. Considering the normal iodine content of the examined tissues, there obviously seems to be two intrathyroidal iodine pools, one of which supplies the body with thyroid hormones under pituitary stimulation even though its thyroglobulin pool is reduced, while a significant amount of the thyroidal iodine pool is bound in metabolically inert protein molecules and therefore increases the goitrogenic effect of iodine deficiency.

[Absorption and pharmacokinetics of large doses of 1-thyroxine in man (author's transl)]. / Resorption und Pharmakokinetik grosser Dosen von 1-Thyroxin beim Menschen

In recent years suppression tests with a single dose of 3 mg 1-thyroxine (T4) and weekly doses of 1 mg T 4 in the treatment of hypothyroidism have been put to clinical trial and the lack of side-effects of such high doses (5 to 15 X daily requirements) was stressed. Hence, it was decided to study the absorption of 1-T-4 from the gastrointestinal tract and its metabolism in euthyroid patients. Doses from 250 to 2500 mug T 4, mixed with 250 muCi 131I-thyroxine were given to 10 patients. After the thyroid had been blocked with perchlorate, the excretion was followed in faeces and urine for 4 to 5 days, the thyroid uptake of 131I was checked and serial blood samples were drawn to follow plasma activity curves. Quantitative analyses of T 4, triiodothyronine (T 3), ETR and TSH were also performed on the plasma samples, whilst paper chromatography of urine samples allowed a further separation of iodide and organic iodine compounds. The results showed a definite rise in plasma T 4 levels after administration of large T 4 doses, with a simultaneous increase in T 3 values. Doses of 2500 mug T 4 temporarily produce abnormally elevated plasma T 4 and ETR values, whilst T 3 increases to the upper limit of the normal range. The relatively moderate reaction of the mentioned parameters following the administration of large T 4 doses can be partly explained by the considerably lower faecal excretion of T 4 with doses of 250 mug T 4 than with high T 4 doses. There is also an intensive binding of T 4 to TBG up to single doses of 1000 mug T 4, which provides an adequate metabolic "buffer" and declines only after saturation of the TBG binding capacity at higher dosage. Moreover, larger doses of T 4 are metabolized quicker than smaller ones. The above-mentioned results allow the following conclusions: 1. Very large single doses of T 4 (2500 to 3000 mug) are less easily absorbed from the gastrointestinal tract than "physiological" doses. 2. The degradation of T 4 at high dosage is quicker than at lower dosage. 3. The intensive binding of T 4 to TBG explains the lack of side effects with large doses of orally-administered T 4. 4. On the basis of the present data single doses of 500 to 1000 mug T 4 can be recommended for therapeutic purposes.